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Table 1.

Multivariate relative risks and their 95% confidence intervals for invasive breast cancer according to quartiles of daily intake of dietary phytoestrogens among 26,868 premenopausal women in the E3N cohort

Dietary intake*Range, μg/dCases (N = 402)Person-years (117,652)Adjusted RR (95% CI)Ptrend§
Total isoflavones 1-22 107 29,799 1.00  
 22-28 78 29,549 0.73 (0.54-0.98)  
 29-35 110 29,097 1.03 (0.79-1.34)  
 36-112 107 29,207 1.00 (0.76-1.31) 0.48 
Coumestrol 63 20,659 1.00  
 0.00-0.02 126 32,317 1.32 (0.97-1.80)  
 0.03-0.05 97 31,944 1.02 (0.74-1.40)  
 0.06-0.60 116 32,732 1.22 (0.89-1.66) 0.68 
Total plant lignans 41-843 101 30,918 1.00  
 844-1,070 106 29,509 1.06 (0.81-1.40)  
 1,071-1,356 91 28,843 0.93 (0.70-1.23)  
 1,357-4,611 104 28,381 1.07 (0.81-1.41) 0.80 
Total enterolignans 168-902 107 30,320 1.00  
 903-1,075 105 29,644 0.99 (0.75-1.30)  
 1,076-1,288 90 28,785 0.86 (0.65-1.14)  
 1,289-3,361 100 28,903 0.94 (0.71-1.24) 0.53 
Dietary intake*Range, μg/dCases (N = 402)Person-years (117,652)Adjusted RR (95% CI)Ptrend§
Total isoflavones 1-22 107 29,799 1.00  
 22-28 78 29,549 0.73 (0.54-0.98)  
 29-35 110 29,097 1.03 (0.79-1.34)  
 36-112 107 29,207 1.00 (0.76-1.31) 0.48 
Coumestrol 63 20,659 1.00  
 0.00-0.02 126 32,317 1.32 (0.97-1.80)  
 0.03-0.05 97 31,944 1.02 (0.74-1.40)  
 0.06-0.60 116 32,732 1.22 (0.89-1.66) 0.68 
Total plant lignans 41-843 101 30,918 1.00  
 844-1,070 106 29,509 1.06 (0.81-1.40)  
 1,071-1,356 91 28,843 0.93 (0.70-1.23)  
 1,357-4,611 104 28,381 1.07 (0.81-1.41) 0.80 
Total enterolignans 168-902 107 30,320 1.00  
 903-1,075 105 29,644 0.99 (0.75-1.30)  
 1,076-1,288 90 28,785 0.86 (0.65-1.14)  
 1,289-3,361 100 28,903 0.94 (0.71-1.24) 0.53 

Abbreviations: RR, relative risk; 95% CI, 95% confidence interval.

*

Total isoflavone intake was computed as the sum of individual isoflavones (genistein, daidzein, formononetin, and biochanin-A), total plant lignans as the sum of individual plant lignans (pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol), and total enterolignans as the sum of individual enterolignans (enterodiol and enterolactone). All were adjusted for energy intake from food (excluding energy from alcohol from total energy intake) by the residual method (24).

The range for each energy-adjusted phytoestrogen quartile was calculated by adding the residual range to the predicted phytoestrogen intake for the mean caloric intake from food (2,149 kcal) for the whole population according to the regression model. Specifically for coumestrol, we computed the lowest category with null values (18%) and higher categories from tertiles of non-null values.

Multivariate RRs and 95% confidence intervals calculated by Cox proportional hazards regression models using age as the time scale and adjusted for years of education (≤12, 13-16, ≥15), height (as continuous variable), body mass index category (as a time-dependent variable according to the height at baseline and the weight at the start of each follow-up interval), age at menarche (<13, 13-14, ≥15 years), personal history of benign breast disease (including fibrocystic breast disease, mastosis, and adenoma) or lobular carcinoma in situ (yes or no), family history of breast cancer in first- or second-degree relatives (yes or no), lifetime use of oral contraceptive (yes or no), age at first full-term pregnancy (FFTP) and parity (nulliparous, age at FFTP <30 years and 1-2 children, age at FFTP <30 years and ≥3 children, or age at FFTP ≥30 years whatever the number of children), geographic area, alcohol consumption (as continuous variable), and dietary energy intake from food.

§

Test for linear trend using median values in each quartile as an ordinal variable.

To account for the lack of data for some enterolignan values in the food composition table, we computed enterolignan values from lignan content using conversion factors obtained in vitro (25).

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